NEW YORK, Jan. 28, 2013 /PRNewswire/ -- Keryx Biopharmaceuticals, Inc. (NASDAQ: KERX) today announced successful top-line results from the long-term Phase 3 study of Zerenex (ferric citrate), the Company's ferric iron-based phosphate binder drug candidate, for the treatment of elevated serum phosphorus levels, or hyperphosphatemia, in patients with end-stage renal disease (ESRD) on dialysis. In this study, Zerenex met the study's primary endpoint, described below, demonstrating a highly statistically significant change in serum phosphorus versus placebo over the four-week Efficacy Assessment Period of the study. In addition, Zerenex met the key secondary endpoints of increasing ferritin and transferrin saturation (TSAT) and reducing the use of intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs) versus the active control over the 52-week Safety Assessment Period of the study. This long-term study was the final component of the Company's Phase 3 registration program, which was conducted pursuant to a Special Protocol Assessment (SPA) with the Food and Drug Administration (FDA). In April 2011, the Company reported the positive final dataset from the short-term study component of this Phase 3 registration program. The Company expects to submit a New Drug Application (NDA) with the FDA and a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for Zerenex in the second quarter of 2013.

Study Design

This Phase 3 long-term study was a multicenter, randomized, open-label, safety and efficacy clinical trial in 441 ESRD patients on hemodialysis or peritoneal dialysis. The study consisted of a 2-week washout period followed by a 52-week Safety Assessment Period in which subjects were randomized 2:1 to receive either Zerenex or an active control (Renvela® [sevelamer carbonate] and/or Phoslo® [calcium acetate]). The 52-week Safety Assessment Period was followed by a 4-week Efficacy Assessment Period. During the Efficacy Assessment Period, only those subjects randomized to treatment with Zerenex during the Safety Assessment Period were randomized in a 1:1 ratio to either continue treatment with Zerenex or switch to placebo for a 4-week treatment period. Subjects were titrated during the study to achieve serum phosphorus levels that ranged between 3.5 to 5.5 mg/dL.

The primary objectives of this study were to determine the long-term safety of KRX-0502 (ferric citrate) in subjects with ESRD undergoing either hemodialysis or peritoneal dialysis, and the efficacy of Zerenex following 52 weeks of treatment in a four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period. Zerenex was administered using a 1 gram oral caplet formulation.

Oral iron therapy was not permitted during the course of the study. IV iron therapy was not permitted if a subject's serum ferritin level was greater than 1,000 ng/mL or the transferrin saturation (TSAT) was greater than 30%. The use of ESAs was at the physician's discretion.

Primary Efficacy Endpoint

The primary efficacy endpoint of this trial was the mean change in serum phosphorus from baseline (Week 52) to end of the four-week Efficacy Assessment Period (Week 56) versus placebo in the Intent-to-Treat (ITT) group. The ITT group included 183 subjects, representing all subjects who took at least one dose of Zerenex or placebo in the Efficacy Assessment Period and provided at least one post-baseline efficacy assessment.

Zerenex met the primary efficacy endpoint with a highly statistically significant result (p<0.0001).

Mean Serum Phosphorus (mg/dL)

Placebo

(n=91)

Zerenex

(n=92)

Baseline (Week 52)

5.3

5.2

End of Treatment1 (Week 56)

7.2

4.9

Change from Baseline at Week 56

1.9

-0.3

Least Squares (LS) Mean Difference from Placebo2

p-value2

-2.3

p<0.0001

1 Last observation carried forward was used for missing data. 2 The LS Mean treatment difference and p-value is created via an ANCOVA model with treatment as the fixed effect and baseline as the covariate.

In addition, as agreed to with the European Medicines Agency (EMA), the treatment difference between Zerenex and Renvela® (sevelamer carbonate) at Week 12 of the Safety Assessment Period in terms of change from baseline (Day 0) in serum phosphorus was analyzed. Zerenex successfully achieved the non-inferiority endpoint versus Renvela®.

Key Secondary Efficacy Endpoints Related to Iron

The objectives of the key iron-related secondary endpoints, which were all pre-specified in the statistical analysis plan, were to corroborate prior data which suggested that Zerenex may increase iron storage parameters and reduce the need for IV iron and/or ESAs. Zerenex met all the key secondary efficacy endpoints related to iron with statistically significant treatment differences versus the active control group (Renvela® [sevelamer carbonate] and/or Phoslo® [calcium acetate]), as follows:

Mean Change in Ferritin

Zerenex demonstrated a statistically significant treatment difference versus the active control group in mean change in serum ferritin from baseline (Day 0) to Week 52.